The bacterial signal molecule, ppGpp, regulates Salmonella virulence gene expression.

Numerous, overlapping global regulatory systems mediate the environmental signalling controlling the virulence of Salmonella typhimurium. With both extra- and intracellular lifestyles, unravelling the mechanisms involved in regulating Salmonella pathogenesis has been complex. Here, we report a factor co-ordinating environmental signals with global regulators involved in pathogenesis. An S. typhimuriumDeltarelADeltaspoT strain deficient in guanosine tetraphosphate (ppGpp) synthesis was found to be highly attenuated in vivo and non-invasive in vitro. The DeltarelADeltaspoT strain exhibited severely reduced expression of hilA and invF, encoding major transcriptional activators required for Salmonella pathogenicity island 1 (SPI-1) gene expression and at least two other pathogenicity islands. None of the growth conditions intended to mimic the intestinal milieu was capable of inducing hilA expression in the absence of ppGpp. However, the expression of global regulators of Salmonella virulence, RpoS and PhoP/Q, and RpoS- and PhoP/Q-dependent, non-virulence-related genes was not significantly different from the wild-type strain. The results indicate that ppGpp plays a central role as a regulator of virulence gene expression in S. typhimurium and implicates ppGpp as a major factor in the environmental and host-dependent regulation of Salmonella pathogenesis.

Pizarro-Cerdá J ，Tedin K 《MOLECULAR MICROBIOLOGY》

Implication of quorum sensing in Salmonella enterica serovar typhimurium virulence: the luxS gene is necessary for expression of genes in pathogenicity island 1.

Choi J ，Shin D ，Ryu S 《-》

Differences in the carriage and the ability to utilize the serotype associated virulence plasmid in strains of Salmonella enterica serotype Typhimurium investigated by use of a self-transferable virulence plasmid, pOG669.

Olsen JE ，Brown DJ ，Thomsen LE ，Platt DJ ，Chadfield MS ... -  《MICROBIAL PATHOGENESIS》

SseL is a salmonella-specific translocated effector integrated into the SsrB-controlled salmonella pathogenicity island 2 type III secretion system.

Bacterial pathogens use horizontal gene transfer to acquire virulence factors that influence host colonization, alter virulence traits, and ultimately shape the outcome of disease following infection. One hallmark of the host-pathogen interaction is the prokaryotic type III secretion system that translocates virulence factors into host cells during infection. Salmonella enterica possesses two type III secretion systems that are utilized during host colonization and intracellular replication. Salmonella pathogenicity island 2 (SPI2) is a genomic island containing approximately 30 contiguous genes required to assemble a functional secretion system including the two-component regulatory system called SsrA-SsrB that positively regulates transcription of the secretion apparatus. We used transcriptional profiling with DNA microarrays to search for genes that coregulate with the SPI2 type III secretion machinery in an SsrB-dependent manner. Here we report the identification of a Salmonella-specific translocated effector called SseL that is required for full virulence during murine typhoid-like disease. Analysis of infected macrophages using fluorescence-activated cell sorting revealed that sseL is induced inside cells and requires SsrB for expression. SseL is retained predominantly in the cytoplasm of infected cells following translocation by the type III system encoded in SPI2. Animal infection experiments with sseL mutant bacteria indicate that integration of SseL into the SsrB response regulatory system contributes to systemic virulence of this pathogen.

Coombes BK ，Lowden MJ ，Bishop JL ，Wickham ME ，Brown NF ，Duong N ，Osborne S ，Gal-Mor O ，Finlay BB ... -  《-》

TolC, but not AcrB, is involved in the invasiveness of multidrug-resistant Salmonella enterica serovar Typhimurium by increasing type III secretion system-1 expression.

The AcrAB-TolC efflux system is involved in multidrug and bile salt resistances. In addition, this pump has recently been suggested to increase the invasion of Salmonella enterica serovar Typhimurium (S. Typhimurium) into host cells in vitro and could therefore have an important clinical relevance for multidrug-resistant strains. The aim of this study was to investigate the role of the TolC outer membrane channel and the AcrB transporter in the interaction of multidrug-resistant S. Typhimurium strains with eukaryotic cells, especially in relation to the expression of the type III secretion system-1 (TTSS-1) required for Salmonella invasion. Deletion of tolC led to a reduced transcription of the Salmonella pathogenicity island-1 genes sipA, invF and hilA, demonstrating that all genes required for TTSS-1 biosynthesis are down-regulated in this mutant. Consequently, tolC mutants secreted smaller amounts of the TTSS-1 effector proteins SipA and SipC, and invasion tests performed with one mutant showed that it was significantly less able to invade HT-29 epithelial cells than its parental strain. This control seems specific to the TTSS-1 among the three TTSS of Salmonella as no down-regulation of expression of TTSS-2 or flagella was observed in this mutant. By contrast, acrB mutants behaved as their parents except that they secrete a slightly greater amount of SipA and SipC proteins. These data indicate that TolC but not AcrB mediates the uptake of multidrug-resistant S. Typhimurium into target host cells. Therefore, this role of TolC in the invasion of the intestine in addition to its role in bile salt resistance reinforces the interest of targeting TolC for fighting multidrug-resistant Salmonella.

Virlogeux-Payant I ，Baucheron S ，Pelet J ，Trotereau J ，Bottreau E ，Velge P ，Cloeckaert A ... -  《-》